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Research Update
RESEARCH UPDATE
“Decorated” Virus Particles May Enhance MRI Capabilities
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esearchers have made chemical modifications to nanometer sized virus particles that have the potential to improve magnetic resonance imaging (MRI) techniques. Their results are reported in the 14 June 2006 issue of Nano Letters. Contrast agents are chemical compounds that enhance the ability of medical imaging techniques, such as MRI, to discriminate between different tissue types. The protein coats of viruses provide an attractive platform for tailoring the physical properties and functions of molecular assemblies because they contain a large number of chemically reactive groups organized in a precise array. Researchers have sought to enhance MRI capabilities through the use of similar large molecular assemblies by increasing the size, and therefore the signal, of MRI contrast agents. The researchers were able to show the attachment of a large number of gadolinium chelates—the chemical compound used in MRI contrast agents—on the surface of a bacteriophage particles. This resulted in the generation of a very intense signal when imaged in a clinical MRI scanner. Previous studies have predicted that as you increase the particle size of an MR contrast agent, it will become more effective. As the particle takes longer to tumble in solution, it should become more capable of influencing the response of neighboring water molecules. The new study provides evidence for this effect. Since the signal that radiologists observe in MRI scans is generated primarily from water molecules within the body, the new method may provide a way to get better contrast and clearer images that can distinguish between different tissue types.
MOLECULAR THERAPY Vol. 14, No. 2, August 2006 Copyright © The American Society of Gene Therapy
According to author, Kent Kirshenbaum, "If a radiologist wants to design a versatile probe that can be used in a variety of different imaging protocols, a chemically modified virus particle now appears to be an attractive option for this type of sophisticated application. For example, if we can decorate the particles so that they are recognized by specific receptors on cell surfaces, we may be able to use MRI to image tumors much smaller than can currently be seen." Nano Letters, online edition, doi: 10.1021/nl060378g
AAV Vector Treats Behavioral Deficit in Transgenic HD Mice
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orkers have successfully used gene therapy to preserve motor function and stop the changes that occur in the brains of mice with Huntington’s disease (HD). Results of the study were published in the 13 June 2006 issue of the Proceedings of the National Academy of Sciences. Huntington’s disease (HD) is a fatal, genetic, neurological disorder resulting from a trinucleotide repeat expansion in the gene that encodes for the protein huntingtin. The authors used an AAV vector to deliver a gene encoding glial-derived neurotrophic factor (GDNF) directly to the brain cells of a mouse transgenic model of the disease. While the authors had previously demonstrated that delivery of GDNF provided structural and functional neuroprotection in a rat neurotoxin model of HD, they now show that viral delivery of GDNF into the striatum of presymptomatic animals ameliorates behavioral deficits in HD mice. The authors wrote "Although GDNF's exact role in preventing cell death in mice modeled with HD remains to be established, we specu-
late the increase trophic support and inhibiting apoptosis (programmed cell death) via these two pathways likely played integral roles." Author Jeffrey Kordower says the study suggests a new approach to forestall disease progression in newly diagnosed HD patients by delivering potent trophic factors with effects that are long-term and nontoxic. GDNF is related to a factor called neurturin (NTN) that is being tested by Ceregene, Inc. (AAN-NTN, also called CERE-120) as a potential treatment for several neurodegenerative diseases. Ceregene's lead program with CERE-120 is in Parkinson’s disease (PD). The company completed enrollment of a Phase I trial with CERE-120. Initial efficacy results of this Phase I trial are expected to be presented this fall and a double-blinded, controlled Phase II trail in PD patients is planned for late 2006. The Proceedings of the National Academy of Sciences USA, online edition, doi: 10.1073/pnas.0508875103
Submit Your Article to Molecular Therapy Today! We Offer Rapid Turnaround: Time to First Decision: Three Weeks Response to Presubmission Enquiries: Forty-eight Hours Email Us at [email protected]
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“Decorated” Virus Particles May Enhance MRI Capabilities
R
esearchers have made chemical modifications to nanometer sized virus particles that have the potential to improve magnetic resonance imaging (MRI) techniques. Their results are reported in the 14 June 2006 issue of Nano Letters. Contrast agents are chemical compounds that enhance the ability of medical imaging techniques, such as MRI, to discriminate between different tissue types. The protein coats of viruses provide an attractive platform for tailoring the physical properties and functions of molecular assemblies because they contain a large number of chemically reactive groups organized in a precise array. Researchers have sought to enhance MRI capabilities through the use of similar large molecular assemblies by increasing the size, and therefore the signal, of MRI contrast agents. The researchers were able to show the attachment of a large number of gadolinium chelates—the chemical compound used in MRI contrast agents—on the surface of a bacteriophage particles. This resulted in the generation of a very intense signal when imaged in a clinical MRI scanner. Previous studies have predicted that as you increase the particle size of an MR contrast agent, it will become more effective. As the particle takes longer to tumble in solution, it should become more capable of influencing the response of neighboring water molecules. The new study provides evidence for this effect. Since the signal that radiologists observe in MRI scans is generated primarily from water molecules within the body, the new method may provide a way to get better contrast and clearer images that can distinguish between different tissue types.
MOLECULAR THERAPY Vol. 14, No. 2, August 2006 Copyright © The American Society of Gene Therapy
According to author, Kent Kirshenbaum, "If a radiologist wants to design a versatile probe that can be used in a variety of different imaging protocols, a chemically modified virus particle now appears to be an attractive option for this type of sophisticated application. For example, if we can decorate the particles so that they are recognized by specific receptors on cell surfaces, we may be able to use MRI to image tumors much smaller than can currently be seen." Nano Letters, online edition, doi: 10.1021/nl060378g
AAV Vector Treats Behavioral Deficit in Transgenic HD Mice
W
orkers have successfully used gene therapy to preserve motor function and stop the changes that occur in the brains of mice with Huntington’s disease (HD). Results of the study were published in the 13 June 2006 issue of the Proceedings of the National Academy of Sciences. Huntington’s disease (HD) is a fatal, genetic, neurological disorder resulting from a trinucleotide repeat expansion in the gene that encodes for the protein huntingtin. The authors used an AAV vector to deliver a gene encoding glial-derived neurotrophic factor (GDNF) directly to the brain cells of a mouse transgenic model of the disease. While the authors had previously demonstrated that delivery of GDNF provided structural and functional neuroprotection in a rat neurotoxin model of HD, they now show that viral delivery of GDNF into the striatum of presymptomatic animals ameliorates behavioral deficits in HD mice. The authors wrote "Although GDNF's exact role in preventing cell death in mice modeled with HD remains to be established, we specu-
late the increase trophic support and inhibiting apoptosis (programmed cell death) via these two pathways likely played integral roles." Author Jeffrey Kordower says the study suggests a new approach to forestall disease progression in newly diagnosed HD patients by delivering potent trophic factors with effects that are long-term and nontoxic. GDNF is related to a factor called neurturin (NTN) that is being tested by Ceregene, Inc. (AAN-NTN, also called CERE-120) as a potential treatment for several neurodegenerative diseases. Ceregene's lead program with CERE-120 is in Parkinson’s disease (PD). The company completed enrollment of a Phase I trial with CERE-120. Initial efficacy results of this Phase I trial are expected to be presented this fall and a double-blinded, controlled Phase II trail in PD patients is planned for late 2006. The Proceedings of the National Academy of Sciences USA, online edition, doi: 10.1073/pnas.0508875103
Submit Your Article to Molecular Therapy Today! We Offer Rapid Turnaround: Time to First Decision: Three Weeks Response to Presubmission Enquiries: Forty-eight Hours Email Us at [email protected]
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